Diabetes mellitus is a major public health problem. In the United States, there are approximately 8 to 10 million patients with diabetes. Diabetes is a syndrome that is caused by a relative or an absolute lack of insulin. Clinically, it is characterized by symptomatic glucose intolerance as well as alterations in lipid and protein metabolism. The maintenance of normal blood sugar levels is achieved by the actions of several hormones, most notably insulin, but also glucagon, epinephrine, corticosteroids, and growth hormone. Hypoglycemia, or low blood sugar, is characterized by below normal levels of blood glucose. On the other hand, hyperglycemia is exemplified by higher than normal concentrations of glucose in the blood. The pancreas produces insulin which is released in response to increased blood glucose concentrations. Insulin works to lower the blood sugar level by stimulating the uptake of glucose by cells. Glucose is used in cellular metabolism to produce energy, or is converted to glycogen for storage in the liver and muscles, or is used in the production of triglycerides and fats.
Hyperglycemia is associated with an increased risk for all of the common late complications of diabetes mellitus, which are the major causes of excess morbidity and mortality in diabetics. However, there is no generally applicable and consistently effective means of maintaining plasma glucose fluctuations within a normal range in diabetics, and efforts to do so entail significant risks of causing frequent or severe hypoglycemic episodes. Nevertheless, common treatments include diet management and the use of insulin preparations and oral hypoglycemic agents.
Conventional treatments for diabetes include oral hypoglycemia agent treatments. The two historically used classes of oral hypoglycemic agents are biguanides and sulfonylureas. Biguanides, however, are not currently approved for treatment of diabetes in the United States. Hypoglycemia is the most important complication of sulfonylurea treatment. Sulfonylurea-induced hypoglycemia can be severe and may last or recur for days after treatment is stopped. A mortality rate of 4.3% in patients hospitalized with sulfonylurea-induced hypoglycemia has been reported. Conventional insulin treatment for diabetes also include one or two injections per day of intermediate-acting insulin, with or without smaller added doses of rapid-acting insulin in the same syringe. Complications of insulin treatment include severe hypoglycemia, local allergic reactions, generalized insulin allergy, immunologic insulin resistance and local fat cell atropy or hypertrophy.
A composition which consists of a Sephadex G-25 column fraction isolated from a 0.1N ammonium hydroxide (base) extract of Polygonum multiflorum has been disclosed for treating hyperglycemia (U.S. Pat. No. 5,531,991). Polygonum multiflorum is also known as HeShouWu, or Chinese Cornbind. The natural distribution of P. multiflorum is in southwestern China, Japan, and Taiwan. It also has been reported to be effective against high blood pressure and hardening of the veins and arteries. (Chinese Herbal Medicine, McClellan Maitland Eds. (1990) p. 150). The disadvantages of using a base extract include that handling base in the manufacturing procedure is hazardous and should be avoided if possible. Furthermore, additional acidic components from the raw material are extracted. The acidic components increase the impurities in the extract and are not useful for human or animal consumption without further modification.
Considering the complications attendant to the use of insulin preparations and sulfonylureas in controlling blood glucose concentrations, there is a need for a new method and a new composition for treating hyperglycemia to control the high blood glucose levels associated with glucose intolerance. The new composition ideally is easy to manufacture and relatively inexpensive.
Relevant Literature
Chinese herbs have long been used in the treatment of many diseases. Modern day descriptions of Chinese herbs and their traditional usage can be found in Lu, Henry C., Legendary Chinese Healing Herbs (1991) and Reid, Daniel P., Chinese Herbal Medicine (1990).
U.S. Pat. No. 5,531,991 discloses a composition which consists of a Sephadex G-25 column fraction isolated from a 0.1N NH.sub.4 OH extract of Polygonum multiflorum; and a method of using such a composition for treating hyperglycemia. Cheng et al (FASEB J. 2, A1103, 1988) report that the He Shou Wu (Polygonum multiflorum) extracted by 0.1 N NH.sub.4 OH (1:20 dilution) has both an insulin-potentiating and a hypocholesterolemic effect in mice. Both references disclose a base extract of Polygonum multiflorum, but not a water extract. Kahn et al (Biol. Trace Element Res. 24, 183 (1990) disclose that the supernatant of cinnamon spice extracted with 0.1 N NH.sub.4 OH (1:20, W/V) contains insulin potentiating activity.
U.S. Pat. No. 5,607,679 discloses a method of treatment of a skin disease associated with hyperproliferation of keratinocytes by administering to a patient an effective amount of Agaricus bisporus lectin. U.S. Pat. No. 5,639,470 discloses a method of deodorizing an animal comprising preparing a deodorant composition by a process of extracting Agaricus bisporus with a hydrophilic solvent to obtain an extract capable of deodorizing the animal; contacting said extract with a suitable carrier; and causing the animal to ingest said extract and said suitable carrier. Neither of the two references relates to insulin potentiating activity.
U.S. Pat. No. 5,175,156 discloses a method for treating undesirably high levels of blood serum lipids in an individual using a composition consisting essentially of chromium tripicolinate. Striffer et al (Metabolism, 44:1314:1320 (1995) report that chromium supplementation prevents insulin-secretory hyper-responsiveness produced in rats fed with a high-sucrose, low chromium diet and conclude that dietary chromium is required for maintenance of normal glucose tolerance in rats. Evans (Int. J. Biosocial Med Res. et al. 11: 163-180 (1989)) report that oral chromium supplements alone provide an improvement of insulin function in the non-diabetic animal. Chromium has been reported to potentiate insulin action, decrease glucose intolerance, decrease total cholesterol, LDL-cholesterol and triglyceride levels and increase HDL-cholesterol level (Anderson, J. Adv. Medicine 1:34-47 (1995).